Elsevier

Journal of Infection

Volume 78, Issue 1, January 2019, Pages 35-39
Journal of Infection

Outcomes of patients with drug-resistant-tuberculosis treated with bedaquiline-containing regimens and undergoing adjunctive surgery

https://doi.org/10.1016/j.jinf.2018.08.003Get rights and content

Highlights

  • Treating MDR-TB is complicated, long and expensive.

  • Bedaquiline (BQ) is a new active drug to treat MDR-TB.

  • No study evaluated safety and effectiveness of surgery in BQ-treated patients.

  • 57 BQ-exposed cases resistant to 7 drugs (median) underwent surgery in 9 countries.

  • 60% of cases initiated BQ after surgery, 36.4% before and completed it afterwards.

  • 90% culture-converted and 69.1% achieved treatment success at the end of treatment.

Summary

Objectives

No study evaluated the contribution of adjunctive surgery in bedaquiline-treated patients. This study describes treatment outcomes and complications in a cohort of drug-resistant pulmonary tuberculosis (TB) cases treated with bedaquiline-containing regimens undergoing surgery.

Methods

This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries between January 2007 and March 2015.

Patients who had surgical indications in a bedaquiline-treated programme-based cohort were selected and surgery-related information was collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes. Treatment outcomes were evaluated according to the time of surgery.

Results

57 bedaquiline-exposed cases resistant to a median of 7 drugs had indication for surgery (52 retreatments; 50 extensively drug-resistant (XDR) or pre XDR-TB). Sixty percent of cases initiated bedaquiline treatment following surgery, while 36.4% underwent the bedaquiline regimen before surgery and completed it after the operation. At treatment completion 90% culture-converted with 69.1% achieving treatment success; 21.8% had unfavourable outcomes (20.0% treatment failure, 1.8% lost to follow-up), and 9.1% were still undergoing treatment.

Conclusions

The study results suggest that bedaquiline and surgery can be safely and effectively combined in selected cases with a specific indication.

Introduction

With over 490,000 multidrug-resistant tuberculosis cases (MDR-TB; TB caused by Mycobacterium tuberculosis resistant to at least isoniazid and rifampicin) occurring globally each year, 6.2% of which are XDR-TB (extensively drug-resistant TB: MDR-TB with additional resistance to fluoroquinolones and one second-line injectable), the ‘white plague’ remains a major clinical and public health priority.1, 2, 3, 4

Although higher success rates are achievable,1, 2 the overall proportion of treatment success is sub-optimal, adverse events common, and treatment duration long and expensive.1, 2, 3, 4 Currently, scientific debate focuses on the role of new medications (bedaquiline and delamanid),5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15 and repurposed drugs for the optimal management of difficult-to-treat M/XDR-TB cases.16, 17, 18, 19

Few studies are presently available on the programmatic use of bedaquiline1,4, 5, 6, 7 and no study has evaluated the contribution of adjunctive surgery in bedaquiline-treated patients.20, 21 The aim of this study is to describe treatment outcomes and complications in a cohort of drug-resistant pulmonary TB cases treated with bedaquiline-containing regimens having indication for surgical intervention (the vast majority of them have been operated).

Section snippets

Materials and methods

This retrospective observational study recruited patients treated for TB in 12 centres in 9 countries from January 2007 to March 2015.

Patients who had surgical indications in a bedaquiline-treated programme-based cohort2 were selected and surgery-related information collected. Patient characteristics and surgical indications were described together with type of operation, surgical complications, bacteriological conversion rates, and treatment outcomes (per World Health Organization (WHO)

Results

Fifty-seven cases of drug-resistant TB managed with both surgical indication and bedaquiline-containing regimens were included (52 from the original study plus 4 added from the Russian Federation and 1 from Italy) as follows: Russian Federation (39), South Africa (5), India (4), Italy (3) and Peru (2); Argentina, Australia, Greece, and Sweden contributed with one case.

Overall, 5 cases were new and 52 had been previously treated for M/XDR-TB (37 failures, 15 relapses).

The majority were male

Discussion

We describe for the first time the use of adjunctive surgery in severe M/XDR-TB cases treated with bedaquiline-containing regimen achieving satisfactory outcomes and high bacteriological conversion rates.

Although the treatment success in this sample (69.1%) was lower than in the larger cohort previously reported (77%),2 it is still 10% higher than that reported by WHO.1 In a large systematic review and meta-analysis of 1,572 MDR-TB cases undergoing surgery, long-term treatment success was

Acknowledgments

The paper is part of the ERS/ALAT and the ERS/SBPT collaborative projects (ERS: European Respiratory Society; ALAT: Latin-American Society of Respiratory Medicine; SBPT: Brazilian Society of Pulmonology) and of the operational research plan of the WHO Collaborating Centre for Tuberculosis and Lung Diseases, Tradate, ITA-80, 2017-2020- GBM/RC/LDA. It is also under the umbrella of the Global TB Network hosted by WAidid (World Association for Infectious Diseases and Immunological Disorders).

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declarations of interest

None.

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